This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A determination of the effectiveness of long-term antiviral therapy for chronic hepatitis C (HALT-C) with long-term peginterferon alfa-2a in patients who failed to respond to previous interferon therapy. Chronic hepatitis C, an illness caused by the hepatitis C virus (HCV), affects four million patients in the United States, and results in 10,000 deaths annually. Hepatitis C is the most common cause of liver transplantation and is a major predisposing factor to the development of liver cancer in the U.S.A. Also, hepatitis C produces debilitating fatigue in 12% of patients and a variety of other non-liver problems. This study will try to determine if long-term treatment with interferon can safely prevent the progression of advanced fibrosis to cirhossis in patients with hepatitis C who failed to respond to previous interferon therapy. It will determine if the risk of developing hepatic decompensation and the risk of developing hepatocellular carcinoma are reduced. During this four year treatment program, the specific aims will be to reduce the risk of developing hepatic decompensation, to reduce the need for transplantation, and to reduce the risk of developing liver cancer. Also, it will be determined if the four years of interferon therapy will improve the quality of life in patients with advanced fibrosis or cirrhosis secondary to chronic hepatitis C who failed previous interferon therapy. The study will include 165 adults with documented non-response to the most recent course of interferon. During a screening visit, histories, physical examinations, and blood tests will be done. A questionnaire about drug use, alcohol use, and mental state will be given. A second screening visit for patients who pass the first will consist of the completion of the questionnaire, signing of the consent form, a urinalysis, a liver biopsy, and an ultrasound of the liver. At least eight weeks later, there will be a baseline visit. All patients will be treated with peginterferon alfa-2a once a week alone, or with ribavirin given in two daily doses. Doses are prescribed according to weight. Weeks 2-20, regular CRC visits will take place. At week 20, several tests will be given which will be assessed during weeks 20-24. Patients who have virologic responses at week 20 will be treated through week 48 and followed-up through week 72. ,